Mild traumatic brain injury

Challenges in the Development of Rodent Models of Mild Traumatic Brain Injury

Authors: Dewitt D, Perez-Polo JR Ph D, Hulsebosch C, Dash PK, Robertson CS.

Approximately 75% of traumatic brain injuries (TBI) are classified mild (mTBI). Despite the high frequency of mTBI, it is the least well studied. The prevalence of mTBI among service personnel returning from Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF) and the recent reports of an association between repeated mTBI and the early onset of Alzheimer's and other types of dementias in retired athletes has focused much attention on mTBI. The study of mTBI requires the development and validation of experimental models of mTBI and one of the most basic requirements for an experimental model is that it replicates important features of the injury or disease in humans. mTBI in humans is associated with acute symptoms such as loss of consciousness and pre- and/or posttraumatic amnesia. In addition, although the majority of patients recover within a few months after mTBI, a small but significant number (2.5 - 26%) had Glasgow Outcome Scores in the "moderate disability" range. These mTBI patients experienced long-term effects of mTBI including deficits in speed of information processing, attention and concentration, memory acquisition, retention and retrieval and reasoning and decision-making. Although methods for the diagnosis and evaluation of the acute and chronic effects of mTBI in humans are well established, the same is not the case for rodents, the most widely used animal for TBI studies. Despite the magnitude of the difficulties associated with adapting these methods for experimental mTBI research, they must be surmounted. The identification and testing of treatments for mTBI depends of the development, characterization and validation of reproducible, clinically relevant models of mTBI.

Tissue vulnerability is increased following repetitive mild traumatic brain injury in the rat

Authors: Huang L, Coats JS, Mohd-Yusof A, Yin Y, Assaad S, Muellner MJ, Kamper JE, Hartman RE, Dulcich M, Donovan VM, Oyoyo U, Obenaus A.

Repetitive mild traumatic brain injury (rmTBI) is an important medical concern for active sports and military personnel. Multiple mild injuries may exacerbate tissue damage resulting in cumulative brain injury and poor functional recovery. In the present study, we investigated the time course of brain vulnerability to rmTBI in a rat model of mild cortical controlled impact. An initial mild injury was followed by a second injury unilaterally at an interval of 1, 3, or 7 days. RmTBI animals were compared to single mTBI and sham treated animals. Neuropathology was assessed using multi-modal magnetic resonance imaging (MRI), followed by ex vivo tissue immunohistochemistry. Neurological and behavioral outcomes were evaluated in a subset of animals receiving rmTBI 3 days apart and shams. RmTBI 1 or 3 days apart but not 7 days apart revealed significantly exacerbated MRI-definable lesion volumes compared to single mTBI and shams. Increases in cortical tissue damage, extravascular iron and glial activation assessed by histology/immunohistochemistry correlated with in vivo MRI findings where shorter intervals (1 or 3 days apart) resulted in increased tissue pathology. There were no neurological deficits associated with rmTBI 3 day animals. At 1 mo post-injury, animals with rmTBI 3 days apart showed reduced exploratory behaviors and subtle spatial learning memory impairments were observed. Collectively, our findings suggest that the mildly-impacted brain is more vulnerable to repetitive injury when delivered within 3 days following initial mTBI.

Potentially neuroprotective gene modulation in an in vitro model of mild traumatic brain injury

Authors: Di Pietro V, Amorini AM, Tavazzi B, Hovda DA, Signoretti S, Giza CC, Lazzarino G, Vagnozzi R, Lazzarino G, Belli A.

In this study, we investigated the hypothesis that mild traumatic brain injury (mTBI) triggers a controlled gene program as an adaptive response finalized to neuroprotection, similar to that found in hibernators and in ischemic preconditioning. A stretch injury device was used to produce an equi-biaxial strain field in rat organotypic hippocampal slice cultures at a specified Lagrangian strain of 10 % and a constant strain rate of 20 s(-1). After 24 h from injury, propidium iodide staining, HPLC analysis of metabolites and microarray analysis of cDNA were performed to evaluate cell viability, cell energy state and gene expression, respectively. Compared to control cultures, 10 % stretch injured cultures showed no change in viability, but demonstrated a hypometabolic state (decreased ATP, ATP/ADP, and nicotinic coenzymes) and a peculiar pattern of gene modulation. The latter was characterized by downregulation of genes encoding for proteins of complexes I, III, and IV of the mitochondrial electron transport chain and of ATP synthase; downregulation of transcriptional and translational genes; downregulation and upregulation of genes controlling the synthesis of glutamate and GABA receptors, upregulation of calmodulin and calmodulin-binding proteins; proper modulation of genes encoding for proapoptotic and antiapoptotic proteins. These results support the hypothesis that, following mTBI, a hibernation-type response is activated in non-hibernating species. Unlike in hibernators and ischemic preconditioning, this adaptive gene programme, aimed at achieving maximal neuroprotection, is not triggered by decrease in oxygen availability. It seems rather activated to avoid increase in oxidative/nitrosative stress and apoptosis during a transient period of mitochondrial malfunctioning.

CT overuse for mild traumatic brain injury

Authors: Melnick ER, Szlezak CM, Bentley SK, Dziura JD, Kotlyar S, Post LA.

BACKGROUND: Multiple, validated, evidence-based guidelines exist to inform the appropriate use of computed tomography (CT) to differentiate mild traumatic brain injury (MTBI) from clinically important brain injury and to prevent the overuse of CT. Yet, CT use is growing rapidly, potentially exposing patients to unnecessary ionizing radiation risk and costs. A study was conducted to quantify the overuse of CT in MTBI on the basis of current guideline recommendations.
METHODS:
A retrospective analysis of secondary data from a prospective observational study was undertaken at an urban, Level I emergency department (ED) with more than 90,000 visits per year. For adult patients with minor head injury receiving CT imaging at the discretion of the treating physician, the proportion of cases meeting criteria for CT on the basis of the Canadian CT Head Rule (CCHR), American College of Emergency Physicians (ACEP) Clinical Policy, New Orleans Criteria (NOC), and National Institute for Health and Clinical Excellence (NICE) guidelines was reported.
RESULTS:
All 346 patients enrolled in the original study were included in the analysis. The proportion of cases meeting criteria for CT for each of the guidelines was: CCHR 64.7% (95% confidence interval , 0.60-0.70), ACEP 74.3% (95% CI, 0.70-0.79), NICE 86.7% (95% CI, 0.83-0.90), and NOC 90.5% (95% CI, 0.87-0.94). The odds ratio of the guidelines for predicting positive head CT findings were also reported.
DISCUSSION:
Some 10%-35% of CTs obtained in the ED for MTBI were not recommended according to the guidelines. Successful implementation of existing guidelines could decrease CT use in MTBI by up to 35%, leading to a significant reduction in radiation-induced cancers and health care costs.

Effects of brain contusion on mild traumatic brain injured patients

Authors: Zare MA, Ahmadi K, Zadegan SA, Farsi D, Rahimi-Movaghar V.

Abstract Traumatic brain injury (TBI) is an important health issue with high prevalence. The most common type of TBI is mild traumatic brain injury (MTBI). MTBI is known as a condition with self-limited symptoms; however it could cause some structural abnormalities of brain and become complicated. Visible structural brain damage could have an important effect on recovery after MTBI but the outcome is not fully understood. This study investigated the clinical course of MTBI patients with the existence of contusion in computed tomography (CT) imaging. Fifty patients with MTBI and simultaneous brain contusion in CT scan were enrolled according to specific exclusion criteria in 14 month. Patients were followed up for two weeks after their first arrival for neurosurgical interventions, decreased level of consciousness and other neurological complications. Presence of neurological symptoms increased duration of hospital stay and number of CT scans. Forty-two percent of MTBI patients with contusion did not have any objective neurological signs. Fifty percent returned to the hospital with neurologic symptoms and signs. Leading causes were headache followed by seizure and dizziness. Rehospitalization was increased in the patients with altered level of consciousness. The size of brain contusion increased in two patients without further need for neurosurgical intervention. Contusion alone did not worsen the prognosis of patients in short term follow up and did not cause neurosurgical interventions.

Mild traumatic brain injury and postconcussive syndrome: A re-emergent questioning

Author: Auxéméry Y. 

INTRODUCTION: Blast injuries are psychologically and physically devastating. Notably, primary blast injury occurs as a direct effect of changes in atmospheric pressure caused by a blast wave. The combat-related traumatic brain injuries (TBI) resulting from exposure to explosions is highly prevalent among military personnel who have served in current wars. Traumatic brain injury is a common cause of neurological damage and disability among civilians and servicemen. Most patients with TBI suffer a mild traumatic brain injury with transient loss of consciousness. A controversial issue in the field of head injury is the outcome of concussion.

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